Reprinted from Research in Virology, vol. 144,
1993, pp. 175-177.

LETTER TO THE EDITOR

More than ten years after the acquired immunodeficiency syndrome
(AIDS) burst upon the scene, the origin of this devastating pandemic
remains a mystery. Only two facts about human immunodeficiency virus
(HIV) type 1, the causative agent of most cases of AIDS, are
generally accepted: first, the virus was derived from a precursor
simian retrovirus (Myers et al., 1992; Seale, 1989); second,
the pandemic unleashed by the virus originated in Africa (Grmek,
1990). However, questions about how and when the virus entered the
human population remain unresolved.

Many theories have been proposed to explain the origin of AIDS.
The most popular is the so-called "cut-hunter" hypothesis, in which
an African hunter was parenterally exposed to monkey blood
contaminated with a virus closely related to HIV (Karpas, 1990; Hrdy,
1987). The infected individual then spread the virus throughout
Africa via war, prostitution, unbanization and tribal rituals. The
problem with this theory is that it would take hundreds of years for
HIV to spread in this manner, and AIDS is a relatively recent disease
(Krause, 1992; Huminer et al., 1987). A more likely
explanation for the AIDS pandemic is a massive population exposure to
an HIV-like virus contained in a vaccine.

Such an exposure may have taken place in the Belgian Congo (now
Zaire, Rwanda and Burundi) from 1957 to 1959. An oral polio vaccine
manufactured at the Wistar Institute in Philadelphia was administered
to hundreds of thousands of inhabitants of this area, including
320,000 infants and children (Koprowski, 1960). The vaccine was made
in fresh monkey kidney cells that were known to be contaminated with
at least 18 different simian viruses (Hayflick et al., 1962).
The vaccine itself was found to be contaminated with an "unidentified
nonpoliomyelitis virus" that was never characterized (Sabin,
1959).

Several facts lend support to the polio vaccine hypothesis of the
origin of AIDS. The vaccine was probably developed in fresh monkey
explants from macaque monkeys, although African green monkeys may
also have been used, and the exact monkey species remains uncertain
(Smith, 1990). It is now known that HIV can infect at least one
species of macaque (Agy et al., 1992), and HIV antibodies have
been detected in African green monkeys (Lecatsas and Alexander,
1992). Thus HIV or a precursor virus could have contaminated the
kidney cell cultures. The area where the vaccination program took
place had the highest incidence of AIDS-related diseases in the
"pre-AIDS" 1960s and 1970s (Williams, 1992). This observation is
consistent with exposure of the population to HIV during childhood
prior to dissemination of the virus to other areas during adulthood.
In the Congo vaccine trial, the vaccine was administered by nebulizer
into the pharynx of each infant and child. This method of
administration would expose mucosal cells to the virus and increase
the likelihood of latent infection (Lehner et al., 1991).
Other infectious diseases in the vaccinated population might also
have contributed to an increased susceptibility to an HIV-like virus
contained in the Congo vaccine.

Can this hypothesis be tested, and why should it be tested? The
answer to the first question lies in the freezers at the Wistar
Institute, where samples of the Congo vaccine may still be stored
(Curtis, 1992a). The answer to the second question is more esoteric.
Understanding the evolution of HIV would help in defining the
pathogenesis of AIDS, and it would also yield clues for successful
treatment of the disease (Stricker and Elswood, 1992). In addition,
by learning from the dark side of vaccine history, we might avoid
repeating it.

It has been more than a year since we proposed our polio
vaccine/AIDS hypothesis (in September 1991). During that time, there
have been numerous articles written on the subject, from
Science to the lay press (Curtis, 1992b,c; Cribb, 1992; Cohen,
1992; Fox, 1992). In addition, previous versions of our hypothesis
have come to light as a result of this discussion (Ratner, 1988;
Gillon, 1992). Reactions to the hypothesis have ranged from
excitement and concern to outrage and ridicule. We can only hope that
careful consideration of our hypothesis will give AIDS researchers
further insight into this deadly disease.

Note from the Editorial Board

Dr. Koprowski, whose name and role have been mentioned in the
above letter, is of course encouraged to reply if he wishes to do
so.

However, the Editorial Board of Research in Virology felt it
appropriate to give its own opinion concerning the possibility raised
by Drs. Stricker and Elswood that the origin of the AIDS epidemic may
have been the anti-polio vaccination campaigns carried out in Africa
in the fifties.

It is legitimate to raise questions about the still mysterious
origin of the AIDS epidemic and not to exclude the role of medical
actions.

However, available data indicate that HIV1 is not present, nor is
any related virus (SIV), in wild rhesus macaques and in cynomolgus
monkeys, which were the sources of kidney cultures used to produce
the poliovirus for vaccines up until 1961. Only two macaque colonies
were infected in US Primate Centers in the seventies, with the
so-called SIVmac, probably originating from experimental inoculation
of SIVmm, a virus which infected a colony of African soot mangabeys,
and which seemingly infected some animals of that same species in
Africa.

From 1961 onwards, polio vaccines were prepared from cells derived
from African green monkeys and baboons (this was because of SV40
contamination of rhesus macaques).

Both of these monkey species can be infected by a retrovirus of
the SIV type, but which is different from SIVmac and SIVmm.

Nucleotide sequence analysis of the genomes of these various
primate retroviruses indicates that all of them are very distant from
HIV1 and therefore could not be at the recent origin of the latter
virus.

Moreover, retrospective PCR studies of tissues from a British
sailor who died of AIDS in 1959 indicate the presence of HIV1 in a
European adult already at that time.

The primate virus which is closest to HIV1 is the CPZ virus
isolated from lymphocytes of a chimpanzee captured in Gabon. Since
chimpanzee tissues have never been used for poliovirus production, it
is difficult to imagine how massive contamination of polio vaccines
by a virus rarely detectable in chimpanzees could have occurred.